Spatio-temporal mapping cortical neuroplasticity in carpal tunnel syndrome

Martinos Center for Biomedical Imaging, MGH-CNY, Building 149, 13th Street, Room 2301, Charlestown, MA 02129, USA,. .
Brain (Impact Factor: 9.2). 10/2012; 135(Pt 10):3062-73. DOI: 10.1093/brain/aws233
Source: PubMed


Neuroimaging data demonstrate that carpal tunnel syndrome, a peripheral neuropathy, is accompanied by maladaptive central neuroplasticity. To further investigate this phenomenon, we collected magnetoencephalography data from 12 patients with carpal tunnel syndrome and 12 healthy control subjects undergoing somatosensory stimulation of the median nerve-innervated Digits 2 and 3, as well as Digit 5, which is innervated by the ulnar nerve. Nerve conduction velocity and psychophysical data were acquired to determine whether standard clinical measures correlated with brain response. In subjects with carpal tunnel syndrome, but not healthy controls, sensory nerve conduction velocity for Digits 2 and 3 was slower than Digit 5. However, somatosensory M20 latencies for Digits 2 and 3 were significantly longer than those of Digit 5. The extent of the M20 delay for median nerve-innervated Digit 2 was positively correlated with decreasing nerve conduction velocity and increasing pain severity. Thus, slower peripheral nerve conduction in carpal tunnel syndrome corresponds to greater delays in the first somatosensory cortical response. Furthermore, spectral analysis demonstrated weaker post-stimulus beta event-related desynchronization and earlier and shorter event-related synchronization in subjects with carpal tunnel syndrome. The extent of the decreased event-related desynchronization for median nerve-innervated digits was positively correlated with paraesthesia severity. We propose that ongoing paraesthesias in median nerve-innervated digits render their corresponding sensorimotor cortical areas 'busy', thus reducing their capacity to process external stimulation. Finally, subjects with carpal tunnel syndrome demonstrated a smaller cortical source separation for Digits 2 and 3 compared with healthy controls. This supports our hypothesis that ongoing paraesthesias promote blurring of median nerve-innervated digit representations through Hebbian plasticity mechanisms. In summary, this study reveals significant correlation between the clinical severity of carpal tunnel syndrome and the latency of the early M20, as well as the strength of long latency beta oscillations. These temporal magnetoencephalography measures are novel markers of neuroplasticity in carpal tunnel syndrome and could be used to study central changes that may occur following clinical intervention.

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Available from: Vitaly Napadow, Jan 05, 2016
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    • "For instance, functional MRI studies have found reduced distance between cortical representations of the second and third digits (D2/ D3) in subjects with CTS and in addition, prolonged sensory conduction velocities for median nerve innervated digits (Napadow et al., 2006). This contracted D2/D3 separation distance for subjects with CTS was recently confirmed by our magneto-encephalography study in a separate patient cohort (Dhond et al., 2012). Furthermore, alterations in neuroplasticity with CTS may also extend to structural properties of S1 grey matter. "
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    ABSTRACT: Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits. Recent reports have shown that this syndrome is also characterized by functional and structural neuroplasticity in the primary somatosensory cortex of the brain. However, the linkage between this neuroplasticity and the functional deficits in carpal tunnel syndrome is unknown. Sixty-three subjects with carpal tunnel syndrome aged 20-60 years and 28 age- and sex-matched healthy control subjects were evaluated with event-related functional magnetic resonance imaging at 3 T while vibrotactile stimulation was delivered to median nerve innervated (second and third) and ulnar nerve innervated (fifth) digits. For each subject, the interdigit cortical separation distance for each digit's contralateral primary somatosensory cortex representation was assessed. We also evaluated fine motor skill performance using a previously validated psychomotor performance test (maximum voluntary contraction and visuomotor pinch/release testing) and tactile discrimination capacity using a four-finger forced choice response test. These biobehavioural and clinical metrics were evaluated and correlated with the second/third interdigit cortical separation distance. Compared with healthy control subjects, subjects with carpal tunnel syndrome demonstrated reduced second/third interdigit cortical separation distance (P < 0.05) in contralateral primary somatosensory cortex, corroborating our previous preliminary multi-modal neuroimaging findings. For psychomotor performance testing, subjects with carpal tunnel syndrome demonstrated reduced maximum voluntary contraction pinch strength (P < 0.01) and a reduced number of pinch/release cycles per second (P < 0.05). Additionally, for four-finger forced-choice testing, subjects with carpal tunnel syndrome demonstrated greater response time (P < 0.05), and reduced sensory discrimination accuracy (P < 0.001) for median nerve, but not ulnar nerve, innervated digits. Moreover, the second/third interdigit cortical separation distance was negatively correlated with paraesthesia severity (r = -0.31, P < 0.05), and number of pinch/release cycles (r = -0.31, P < 0.05), and positively correlated with the second and third digit sensory discrimination accuracy (r = 0.50, P < 0.05). Therefore, reduced second/third interdigit cortical separation distance in contralateral primary somatosensory cortex was associated with worse symptomatology (particularly paraesthesia), reduced fine motor skill performance, and worse sensory discrimination accuracy for median nerve innervated digits. In conclusion, primary somatosensory cortex neuroplasticity for median nerve innervated digits in carpal tunnel syndrome is indeed maladaptive and underlies the functional deficits seen in these patients.
    Preview · Article · Apr 2014 · Brain
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    • "CTS is mainly driven by partial deafferentation secondary to the compression of the median nerve within the carpal tunnel (Kiernan et al., 1999). In addition to the peripheral sensorimotor manifestations of CTS, cortical digit representations in the brain display expansion, amplification, and/or shifted locus in the primary somatosensory cortex (S1), as evaluated by both fMRI (Napadow et al., 2006, 2007; Zanette et al., 2006) and MEG (Dhond et al., 2012; Tecchio et al., 2002). These studies suggest that the function of the entire hierarchy of the somatosensory system from the peripheral to the central sites may be altered in CTS. "
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    ABSTRACT: Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplasticity. We evaluated structural reorganization in brain gray (GM) and white (WM) matter and whether such plasticity is linked to altered median nerve function in CTS. We performed NCV testing, T1-weighted structural MRI, and diffusion tensor imaging (DTI) in 28 CTS and 28 age-matched healthy controls (HC). Voxel-based morphometry (VBM) contrasted regional GM volume for CTS versus HC. Significant clusters were correlated with clinical metrics and served as seeds to define associated WM tracts using DTI data and probabilistic tractography. Within these WM tracts, fractional anisotropy (FA), axial (AD) and radial (RD) diffusivity were evaluated for group differences and correlations with clinical metrics. For CTS subjects, GM volume was significantly reduced in contralesional S1 (hand-area), pulvinar and frontal pole. GM volume in contralesional S1 correlated with median NCV. NCV was also correlated with RD and was negatively correlated with FA within U-fiber cortico-cortical association tracts identified from the contralesional S1 VBM seed. Our study identified clear morphometric changes in the CTS brain. This central morphometric change is likely secondary to peripheral nerve pathology and altered somatosensory afference. Enhanced axonal coherence and myelination within cortico-cortical tracts connecting primary somatosensory and motor areas may accompany peripheral nerve deafferentation. As structural plasticity was correlated with NCV and not symptomatology, the former may be a better determinant of appropriate clinical intervention for CTS, including surgery.
    Full-text · Article · Feb 2013 · Clinical neuroimaging
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    ABSTRACT: The genetic influence of Val158Met polymorphisms, one of the potential genetic determinants for nociceptive processing, has not been previously investigated in women with carpal tunnel syndrome (CTS). To investigate the association between the Val158Met polymorphism with CTS and to assess the relationship between the Val158Met polymorphism and the clinical outcomes and widespread pressure pain hypersensitivity in women with CTS. Case control study. Neurology department at an urban hospital. One hundred nine (n = 109) women (mean age: 47 ± 9 years) with a clinical and electrodiagnostic diagnosis of CTS and 109 matched healthy women participated. After amplifying the Val158Met polymorphism by polymerase chain reactions, rs4680 genotype frequencies and allele distributions were calculated. We classified individuals according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. The intensity of the pain was assessed with a numeric rating scale (0-10) and disability was determined with the Boston Carpal Tunnel Questionnaire. Pressure pain thresholds were bilaterally assessed over median, radial, and ulnar nerve trunks; C5-C6 facet joints; and carpal tunnel and tibialis anterior muscles.Institutional Review Board: The study project was approved by the local human research committee (HUFA-12/14). All participants signed an informed consent prior to their inclusion in the study. The distribution of the 3 Val158Met genotypes (Val/Val, Val/Met, Met/Met) and alleles was not significantly different between women with CTS and healthy women (Chi-Square = 0.498; P = 0.780). Women with CTS carrying the Met/Met genotype showed higher levels of pain and disability than those with the Val/Met genotype (P < 0.01) and with the Val/Val genotype (P < 0.001). No differences in the years with pain (P = 0.954), age (P = 0.740), depression (P = 0.530), severity of CTS (P = 0.744) or presence of unilateral-bilateral symptoms (P = 0.279) existed depending on the rs4680 Val158Met genotype. No significant differences in widespread pressure pain sensitivity were observed in any of the points depending on the rs4680 Val158Met genotype (P > 0.315). We only recruited women from a specialized department. Current results indicated that the Val158Met polymorphism seems not to be a risk factor for the development of CTS; however, it was associated with increased perception of pain and higher disability scores.
    No preview · Article · Sep 2013 · Pain physician
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